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PubMed2004

Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer's disease using cortical pattern matching: diagnosis and gender effects.

We used magnetic resonance imaging (MRI) and cortical pattern matching to map differences in cortical gray matter deficits between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and explored the possible influence of gender on these patterns. Twenty-nine patients with AD (age 77.9 +/- 5.5), 16 patients with DLB (76.4 +/- 6.7), and 38 controls (75.3 +/- 6.8) were included. Dementia groups were matched for illness severity. Detailed spatial analyses of gray matter were conducted across the entire cerebral cortex by measuring local proportions of gray matter at thousands of homologous cortical surface locations in each subject and between diagnostic groups. To visualize regional changes, statistical differences were mapped at each cortical surface location in 3D. Main effects of diagnosis demonstrated prominent gray matter differences in orbitofrontal and temporal cortices, where AD exhibited the greatest deficits relative to DLB. Main effects of sex showed less gray matter in men within all group comparisons. Exploratory findings for sex by diagnosis interactions suggest greater gray matter loss in the anterior cingulate for men with AD, relative to controls, AD females, and individuals with DLB. Relative preservation of orbitofrontal cortices in addition to temporal structures may contribute to distinguishing DLB from AD. Further investigation of the influence of gender might provide a more comprehensive understanding of the pathophysiological differences underlying the two forms of dementia.

Aged↗
PubMed2005

Unified SPM-ICA for fMRI analysis.

A widely used tool for functional magnetic resonance imaging (fMRI) data analysis, statistical parametric mapping (SPM), is based on the general linear model (GLM). SPM therefore requires a priori knowledge or specific assumptions about the time courses contributing to signal changes. In contradistinction, independent component analysis (ICA) is a data-driven method based on the assumption that the causes of responses are statistically independent. Here we describe a unified method, which combines ICA, temporal ICA (tICA), and SPM for analyzing fMRI data. tICA was applied to fMRI datasets to disclose independent components, whose number was determined by the Bayesian information criterion (BIC). The resulting components were used to construct the design matrix of a GLM. Parameters were estimated and regionally-specific statistical inferences were made about activations in the usual way. The sensitivity and specificity were evaluated using Monte Carlo simulations. The receiver operating characteristic (ROC) curves indicated that the unified SPM-ICA method had a better performance. Moreover, SPM-ICA was applied to fMRI datasets from twelve normal subjects performing left and right hand movements. The areas identified corresponded to motor (premotor, sensorimotor areas and SMA) areas and were consistently task related. Part of the frontal lobe, parietal cortex, and cingulate gyrus also showed transiently task-related responses. The unified method requires less supervision than the conventional SPM and enables classical inference about the expression of independent components. Our results also suggest that the method has a higher sensitivity than SPM analyses.

Adult↗
PubMed2002

Simplified normal mode analysis of conformational transitions in DNA-dependent polymerases: the elastic network model.

The Elastic Network Model is used to investigate the open/closed transition in all DNA-dependent polymerases whose structure is known in both forms. For each structure the model accounts well for experimental crystallographic B-factors. It is found in all cases that the transition can be well described with just a handful of the normal modes. Usually, only the lowest and/or the second lowest frequency normal modes deduced from the open form give rise to calculated displacement vectors that have a correlation coefficient larger than 0.50 with the observed difference vectors between the two forms. This is true for every structural class of DNA-dependent polymerases where a direct comparison with experimental structural data is available. In cases where only one form has been observed by X-ray crystallography, it is possible to make predictions concerning the possible existence of another form in solution by carefully examining the vector displacements predicted for the lowest frequency normal modes. This simple model, which has the advantage to be computationally inexpensive, could be used to design novel kind of drugs directed against polymerases, namely drugs preventing the open/closed transition from occurring in bacterial or viral DNA-dependent polymerases.

Computer Simulation↗
PubMed2001

A competition model with dynamically allocated inhibitor production.

The chemostat is a basic model for competition in an open system and a model for the laboratory bio-reactor (CSTR). Inhibitors in open systems are studied with a view of detoxification in natural systems and of control in bio-reactors. This study allows the amount of resource devoted to inhibitor production to depend on the state of the system. The feasibility of one dependence is provided by quorum sensing. In contrast to the constant allocation case, a much wider set of outcomes is possible including interior, stable rest points and stable limit cycles. These outcomes are important contrasts to competitive exclusion or bistable attractors that are often the outcomes for competitive systems. The model consists of four non-linear ordinary differential equations and computer software is used for most of the stability calculations.

Bioreactors↗
PubMedDate not supplied

A method for approximating fractional power average relaxation times without inversion of multiexponential relaxation data.

A method is presented for approximating fractional power averages of relaxation times for data equispaced in log time, without the need to invert multiexponential relaxation data. This form of average permits giving emphasis to short or long times depending on the choice of the p value, thus giving the possibility of representing different specific properties of porous media. This method has been tested on a large number of nuclear magnetic resonance (NMR) relaxation measurements in porous samples. This new algorithm appears to be robust with respect to both measurement and computation, and its major advantage is that it does not depend on a particular inversion method. Moreover, it permits a very fast computation.

Algorithms↗
PubMed2003

Estimation of bolus dispersion effects in perfusion MRI using image-based computational fluid dynamics.

Bolus tracking magnetic resonance imaging (MRI) is a powerful technique for measuring perfusion, and is playing an increasing role in the investigation of acute stroke. However, limitations have been reported when assessing patients with steno-occlusive disease. The presence of a steno-occlusive disease in the artery may cause bolus dispersion, which has been shown to introduce significant errors in cerebral blood flow (CBF) quantification. Bolus dispersion is commonly described by a vascular transport function, but the function that properly characterizes the dispersion is unknown. A novel method to quantify bolus dispersion errors on perfusion measurements is presented. A realistic patient-specific model is constructed from anatomical and physiologic MR data, and the arterial blood flow pattern and the transport of the bolus of contrast agent are computed using finite element analysis. The methodology presented was used also to evaluate the accuracy of three simple vascular models. The methodology was tested on MR data from two normal subjects and two subjects with mild carotid artery stenosis. The estimated CBF errors were of the order of 15% to 20%. However, the presence of stenosis did not necessarily introduce larger dispersion (not only the geometrical model but also the particular physiologic conditions influence the degree of bolus dispersion). The method described will contribute to a better understanding of errors introduced by dispersion effects, to the assessment and validation of vascular models, and to the development of new methods for the correction of dispersion errors in CBF quantification.

Blood Flow Velocity↗
PubMed1997

Determination of transients and compensation capacities of breath-by-breath analysis by cubic splines.

The development of breath-by-breath analysis during an ergospirometry improved the precision of the measurement. However, the abundance of data yields oscillating curves which make it very difficult to detect exactly the breakpoints, maxima and minima. By using cubic splines one is able to smooth the curve of the primary data without falsifying or distorting it. A breakpoint marks the beginning of a hyperventilation with an nonlinear increase of VE or the beginning of an excess value of CO2. Furthermore, the amount of CO2 required to compensate for the acid-base balance as well as the oxygen debt in the recovery phase can be calculated by the area under the curve.

Algorithms↗
PubMed2001

Peripheral link model as an alternative for pharmacokinetic-pharmacodynamic modeling of drugs having a very short elimination half-life.

Attempts to obtain estimates of pharmacokinetic-pharmacodynamic (PK-PD) parameters for mivacurium with traditional central link models were unsuccessful in many patients. We hypothesized that a link model with the peripheral compartment would be more appropriate for mivacurium in view of its extremely rapid plasma clearance and its potential elimination by tissue pseudocholinesterases. For validation purposes, the peripheral link model was applied to other neuromuscular blocking agents (NMBA), i.e., atracurium and doxacurium which have respectively an intermediate and a long elimination half-life. Assuming peripheral elimination in PK-PD modeling was investigated but found to have no impact on the estimation of PK-PD parameters. Our results indicate that, for drugs having intermediate and long elimination half-lives, EC50 values are similar with either the central or peripheral link model. For mivacurium, a peripheral link model enables PK-PD modeling in all subjects, with more precision in the PK-PD parameter estimates and a better fitting of the effect data when compared to the central link model. For these reasons, a peripheral link model should be preferred for mivacurium.

Adolescent↗
PubMed1998

Evaluation of a Cmin and a normalized Cmin method for the confirmation of steady-state in bioequivalence studies.

PURPOSE: Two methods to confirm attainment of steady-state conditions in multiple-dose bioequivalence studies are described and evaluated: (1) the Cmin method and (2) the Area Below the Cmin plasma-concentration-versus-time-curve method (ABCM method). METHODS: Cmin Method-After repetitive drug administration to presumed steady-state, successive trough, or Cmin, values are evaluated to determine if they are equal. ABCM Method-The ABCM of successive doses from dose two to presumed steady-state [ABCM(ss)] are divided by the ABCM for the first dose, ABCM(t), to give ABCM(ss)/ ABCM(t)=R, which describes the increase in ABCM(n) with successive doses. The quantity, R, is then divided by an accumulation ratio to render the value independent of intra-subject clearance differences. Monte Carlo simulations were done to test the effects of data error and slow-clearing subpopulations on the method's performance. Data from multiple-dose bioequivalence studies were evaluated using confidence intervals for both methods to determine how well each predicted steady-state for immediate-release and controlled-release drug products. RESULTS/CONCLUSIONS: The Cmin method more accurately predicted the attainment of steady-state conditions for immediate-release formulations compared to the ABCM method. Conversely, the ABCM procedure more accurately predicted the attainment of steady-state conditions for controlled-release formulations compared to the Cmin method. The simulation results were further supported by the experimental data.

Adolescent↗
PubMed2003

Blood compatible design of a pulsatile blood pump using computational fluid dynamics and computer-aided design and manufacturing technology.

Thrombus formation is a critical issue when designing a long-term implantable left ventricular assist system (LVAS). Fluid dynamic characteristics of blood flow are one of the main factors that cause thrombus formation. In this study, we optimized the fluid dynamics of a sac blood pump in our LVAS to ensure minimization of shear-related blood damage that could lead to thrombus formation. A pump housing and a sac chamber were designed with computer-aided design (CAD) software, and fluid dynamics were estimated by computational fluid dynamic (CFD) analysis. We adopted distribution of CFD results for qualitative evaluation, and we also tried to estimate normalized index of hemolysis (NIH) from the results of CFD analysis as a quantitative index of optimization for geometry of the blood pump chamber. A prototype model of the optimized blood pump was made using a three-axis computer machine tool by whittling pieces of nonfoamed polyurethane. Shear stress and theoretical NIH in the redesigned model were lower than those in the first model. Area of flow stagnation that was observed in the first model was not seen in the redesigned model. The results demonstrate that application of CAD/CAM technology to design an artificial heart contributes to optimizing a blood pump chamber for the purpose of reducing thrombus formation.

Biomedical Technology↗
PubMed2004

Corneal and retinal temperatures under various ambient conditions: a model and experimental approach.

BACKGROUND: To determine the distribution of temperatures between the cornea and retina under various external conditions, such as illumination and external temperature, using a simplified heat exchange model. MATERIALS AND METHODS: The human eye is modeled as a water sphere surrounded by different heat sources: choroidal and ciliary body blood flow, tears evaporation, metabolic activity, diffuse retinal illumination and external convection. Corneal and retinal temperatures are derived from this model using finite element theory applied to heat transport. Each of five subjects (28 +/- 10 years old) were placed in three different environments: - 20 degrees C, 20 degrees C and 40 degrees C. After 15 mn, their corneal temperatures were measured with an infrared camera. Corneal temperatures are compared with the values obtained from the model, assuming the same blood flow for all environments. RESULTS: 1) Ciliary body and choroid contribute at least 20 times more than retina to the retinal temperature; 2) temperature increase of the retina due to illumination is negligible; 3) a 10 % reduction of choroidal blood flow induces a corneal temperature decrease of 0.2 degrees C at - 20 degrees C and < 0.1 degrees C at 20 degrees C and 40 degrees C. At normal choroidal blood flow, changes in ambient temperature have a negligible effect on retinal temperature. Measured corneal temperatures agreed with the values from the model: 26.4 +/- 0.9 versus 26.8 degrees C, at - 20 degrees C and 36.2 +/- 0.5 versus 36.7 at 40 degrees C. CONCLUSIONS: Our simplified eye model predicts in a satisfactory way measured corneal temperatures under very different conditions. Calculations show that changing external temperatures from - 20 to + 40 degrees C affects the retinal temperature by less than 1.8 degrees C.

Adult↗
PubMed2003

A data mining technique for discovering distinct patterns of hand signs: implications in user training and computer interface design.

Hand signs are considered as one of the important ways to enter information into computers for certain tasks. Computers receive sensor data of hand signs for recognition. When using hand signs as computer inputs, we need to (1) train computer users in the sign language so that their hand signs can be easily recognized by computers, and (2) design the computer interface to avoid the use of confusing signs for improving user input performance and user satisfaction. For user training and computer interface design, it is important to have a knowledge of which signs can be easily recognized by computers and which signs are not distinguishable by computers. This paper presents a data mining technique to discover distinct patterns of hand signs from sensor data. Based on these patterns, we derive a group of indistinguishable signs by computers. Such information can in turn assist in user training and computer interface design.

Algorithms↗
PubMed2006

Is there a similarity between DNA damage in adults with chronic alcoholism and community-dwelling healthy older adults?

AIMS: Daily alcohol consumption and ageing have been linked with DNA damage, leading to the hypothesis that chronic alcoholism causes DNA damage similar to that which occurs with ageing. Likewise, it has been suggested that chronic alcoholism is the cause of accelerated or premature ageing. The objective of this study was to evaluate the frequency and magnitude of DNA damage among adults with chronic alcoholism and healthy older adults residing in Mexico City. METHODS: A cross-sectional and comparative study was carried out in a sample of 53 chronic alcoholics of 25-44 years of age (without alcohol ingestion in the past 30 days) without additional diseases, 26 healthy subjects >or=60 years of age, and 25 healthy adults of 25-44 years of age without alcohol addiction, all residents of Mexico City during the past 10 years. DNA damage was evaluated by single-cell gel electrophoresis technique (Comet assay). RESULTS: Our results showed a similar percentage of DNA damage between healthy elderly subjects and chronic alcoholics (62 vs 55%, P >0.05), although average DNA migration was greater in alcoholics than in the elderly (78.1 +/- 33.2 vs 58.6 +/- 26.2, P = 0.09). However, the percentage of subjects with more than six damaged cells was higher in the older adults subjects group than in the group chronic alcoholics (19 vs 35%, P = 0.16). CONCLUSIONS: Data suggest that DNA damage is not similar in young subjects with chronic alcoholism that which occurs with ageing.

Adult↗
PubMed2001

Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response.

In the bloodstream of its mammalian host, the "slender" form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative "stumpy" form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation.

Animals↗
PubMed2003

Beta edge strands in protein structure prediction and aggregation.

It is well established that recognition between exposed edges of beta-sheets is an important mode of protein-protein interaction and can have pathological consequences; for instance, it has been linked to the aggregation of proteins into a fibrillar structure, which is associated with a number of predominantly neurodegenerative disorders. A number of protective mechanisms have evolved in the edge strands of beta-sheets, preventing the aggregation and insolubility of most natural beta-sheet proteins. Such mechanisms are unfavorable in the interior of a beta-sheet. The problem of distinguishing edge strands from central strands based on sequence information alone is important in predicting residues and mutations likely to be involved in aggregation, and is also a first step in predicting folding topology. Here we report support vector machine (SVM) and decision tree methods developed to classify edge strands from central strands in a representative set of protein domains. Interestingly, rules generated by the decision tree method are in close agreement with our knowledge of protein structure and are potentially useful in a number of different biological applications. When trained on strands from proteins of known structure, using structure-based (Dictionary of Secondary Structure in Proteins) strand assignments, both methods achieved mean cross-validated, prediction accuracies of approximately 78%. These accuracies were reduced when strand assignments from secondary structure prediction were used. Further investigation of this effect revealed that it could be explained by a significant reduction in the accuracy of standard secondary structure prediction methods for edge strands, in comparison with central strands.

Algorithms↗
PubMed2001

Boundary element method calculation of individual head-related transfer function. II. Impedance effects and comparisons to real measurements.

Following previous work by the author involving the calculation of an individual head-related transfer function (HRTF) using a Boundary Element Method (BEM) approach, impedance conditions are now included to take account of the acoustic properties of human hair. In addition, comparisons are made here between calculations and measured values for the HRTF of a specific individual. Numerous works have been published regarding the measurement of HRTFs, but rarely are several methods compared for the same individual. The results presented in the work compare two different measurement techniques and a computational BEM for acquiring an individual HRTF. Impedance effects have been incorporated in the BEM model for hair based on measured data, providing a final set for comparison. Measurement results show significant variations for the same individual. Computational results show good agreement within the range of experimental variations. Definite trends are observed for many directions, while the limitations of the methods are also highlighted for others. The effects of incorporating hair impedance are shown to provide an improvement in the correlation of computational results, indicating an affect of hair impedance on the HRTF.

Acoustics↗
PubMed2000

Computerized analysis of the likelihood of malignancy in solitary pulmonary nodules with use of artificial neural networks.

PURPOSE: To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) to assist radiologists in the distinction of benign and malignant pulmonary nodules. MATERIALS AND METHODS: Fifty-six chest radiographs of 34 primary lung cancers and 22 benign nodules were digitized with a 0.175-mm pixel size and a 10-bit gray scale. Eight subjective image features were evaluated and recorded by radiologists in each case. A computerized method was developed to extract objective features that could be correlated with the subjective features. An ANN was used to distinguish benign from malignant nodules on the basis of subjective or objective features. The performance of the ANN was compared with that of the radiologists by means of receiver operating characteristic (ROC) analysis. RESULTS: Performance of the ANN was considerably greater with objective features (area under the ROC curve, Az = 0.854) than with subjective features (Az = 0.761). Performance of the ANN was also greater than that of the radiologists (Az = 0.752). CONCLUSION: The computerized scheme has the potential to improve the diagnostic accuracy of radiologists in the distinction of benign and malignant solitary pulmonary nodules.

Adult↗
PubMedDate not supplied

Serial measurements of positron-emitting isotope activity in rat brain.

This report describes the construction and performance characteristics of a device capable of making rapid serial measurement of rat brain radioactivity following the administration of a positron emitting isotope. Two bismuth germanate oxide (BGO) scintillation detectors in a coincidence detection circuit are used to achieve the necessary degree of collimation. Data from the device can be used to characterize cerebral biochemical and physiological processes using computer-assisted mathematical models.

Animals↗